Congenital hypothyroidism in children
Introduction
Introduction to congenital hypothyroidism in children Congenital hypothyroidism (congenital hypothyroidism) is caused by congenital factors that cause thyroid hormone synthesis disorders, reduced secretion, leading to growth disorders in children, intelligent backwardness, congenital hypothyroidism is one of the most common endocrine diseases in pediatrics. basic knowledge The proportion of illness: 0.005% Susceptible people: children Mode of infection: non-infectious Complications: pericardial effusion pleural effusion
Cause
Causes of congenital hypothyroidism in children
(1) Causes of the disease
Congenital hypothyroidism can be divided into two categories: sporadic congenital hypothyroidism and local congenital hypothyroidism. The etiology and incidence of sporadic congenital hypothyroidism are shown in Table 2. More common in thyroid hypoplasia or ectopic, local Sexual congenital hypothyroidism mainly occurs in areas where goiter is endemic, and it is related to iodine deficiency. With the popularity of iodized salt supply, iodine deficiency has been basically controlled in China, but it is also seen in some areas.
According to the serum TSH concentration, congenital hypothyroidism can be divided into:
1. Increased TSH concentration
(1) Primary hypothyroidism: including thyroid deficiency, dysplasia, abnormalities; thyroxine synthesis disorders.
(2) Temporary hypothyroidism: including pregnant mothers taking anti-thyroid drugs; immature children.
2. The TSH concentration is normal
(1) Hypothalamus, pituitary a low.
(2) Low thyroid binding globulin.
(3) Temporary hypothyroidism can be seen in immature children, non-thyroid diseases, etc.
(two) pathogenesis
1. Pathophysiology of the thyroid: In the third week of pregnancy, the fetal thyroid begins with the thyroid primordial tissue protruding from the anterior intestinal epithelial cells. At the 5th week of gestation, the thyroid tongue is atrophied, the thyroid is moved downward from the pharynx, and the thyroid is moved to the 7th week. Normal position in front of the neck, TSH can be measured in the fetal pituitary gland from the 10th week of pregnancy, and TSH can be measured in cord blood from 18 to 20 weeks of gestation.
Fetal thyroid can take up iodine and iodinated tyrosine, coupled into triiodothyronine (T3), thyroxine (T4), and release thyroid hormone to the blood circulation, 8 to 10 weeks of gestation, thyroid Glue appeared in the follicles and began to synthesize T4. The T4 level increased at 20 weeks of gestation, but the TSH, T3, T4, free T3 (FT3) and free T4 (FT4) levels in fetal serum were very low before 20 weeks. Even the test can not pass, the placenta can not pass TSH, rarely through the thyroid hormone, indicating that the pituitary-thyroid axis of the fetus and the mother are independent of each other, until the second trimester, the fetal hypothalamic-pituitary-thyroid axis begins to function, TSH secretion level Increasingly high, continued until delivery, TSH in the mother throughout the pregnancy did not change, the TSH in the amniotic fluid can not be measured under normal conditions, because the fetal blood T4 gradually increased under the influence of TSH, the concentration of thyroxine-binding globulin (TBG) At the same time, anti-thyroid drugs, including radioactive iodine, can pass freely through the placenta, so mothers with hyperthyroidism (referred to as hyperthyroidism) can receive thyroid function in neonates who receive antithyroid drugs during pregnancy. Low herniation with goiter.
The normal value of neonatal TSH changes day by day, shortly after birth, about 30 ~ 90min, due to cold environment stimulation, TSH suddenly rises in the blood, and falls to normal after 3 to 4 days. Under the influence of TSH, T3 and T4 are born. After 24 to 48 hours, the physiological changes of these hormone concentrations can be understood to correctly evaluate the thyroid function in the neonatal period.
2. Synthesis and secretion of thyroid hormones: The synthesis of thyroid hormones is divided into the following steps:
(1) Concentration of iodine in the thyroid: The iodine in the food is absorbed into the blood in the form of inorganic iodide after absorption in the intestine, and is concentrated in the thyroid epithelial membrane by the iodine pump, and the iodide is inorganic iodine.
(2) Oxidation of iodide and iodination of tyrosine: under the action of peroxidase, iodide is oxidized to active iodine and combined with tyrosine to form monoiodotyrosine (MIT) and diiodotyrosine Acid (DIT).
(3) Coupling of iodine tyrosine: Two molecules of DIT are condensed into one molecule of T4, and one molecule of MIT and DIT is condensed into one molecule of T3. Both T4 and T3 are thyroid hormones.
(4) secretion of thyroid hormone: iodine iodine and T3, T4 synthesis, are carried out on the globulin molecule, this globulin is called thyroglobulin (TG), lysosomal protein The action of hydrolase releases T3, T4 and TG, penetrates the cell membrane of the filter and the blood vessel wall into the blood, and exerts physiological effects.
After thyroid hormone is secreted into the blood, most of it binds to plasma proteins. About 75% of T4 and TBG bind, about 15% binds to thyroxine-binding pre-albumin (TBPA), about 10% binds to albumin, and T3 has 65. %~70% binds to TBG, about 8% binds to TBPA, the rest binds to albumin, only 0.03% T4 and 0.3% T3 are in a free state, T3 is 3 to 4 times stronger than T4, and the body needs R 80% is the conversion of T4 by the action of the surrounding tissue 5'-deiodinase.
3. Regulation of thyroid hormone: The function of thyroid is regulated by the concentration of T3 and T4 in the hypothalamus, anterior pituitary and blood. The three constitute a feedback system, and the neurosecretory cells of the hypothalamus produce thyroid stimulating hormone releasing hormone (TRH). Released into the pituitary portal vein, excited TSH in the anterior pituitary, TSH stimulates thyroid secretion T3, T4, free T3 in the blood, T4 is too high, inhibits the secretion of TSH, too low TSH secretion, thereby exciting the thyroid Secretion, the above feedback system keeps the blood balance of T4 and T3 to ensure the normal metabolism and physiological activities of the body.
4. Physiological effects of thyroid hormone
(1) Heat production: Thyroid hormone can stimulate the oxidation of substances, strengthen oxidative phosphorylation and promote metabolism.
(2) Protein metabolism: physiological dose of thyroid hormone increases protein and nucleic acid synthesis, and nitrogen excretion is reduced. If high dose of thyroid hormone is given, protein synthesis is inhibited, and free amino acid concentrations in plasma, liver and muscle are increased.
(3) Glucose metabolism: Thyroid hormone can promote the absorption of glucose and galactose in the small intestine, increase the rate of glucose uptake by adipose tissue and muscle tissue, and enhance the effect of catecholamine and insulin on glucose metabolism, making the cell catecholamine receptor adrenaline. The sensitivity is enhanced.
(4) Fat metabolism: Thyroid hormone can enhance the sensitivity of adipose tissue to catecholamines and glucagon. These hormones act through adenylate cyclase system to activate lipase in cells and promote fat hydrolysis.
(5) Water and salt metabolism: Thyroid hormone has a diuretic effect. When the nail is low, the intercellular fluid increases, and a large amount of albumin and mucin are accumulated, which is called mucinous edema.
(6) For growth and development: Thyroid hormone can promote growth through the synthesis of protein, and synergistic effect with growth hormone in promoting growth. Patients with hypothyroidism grow slowly and bone age is backward.
(7) Promote brain development: The number of fetal brain cells grows fastest in the third trimester of pregnancy, and still grows rapidly in the first year after birth. In the process of brain cell proliferation and differentiation, thyroid hormone is essential, especially in the second half of pregnancy. During the first year of life, it is more important. The earlier the hypothyroidism occurs, the more severe the brain damage is, and it is often irreversible.
Prevention
Prevention of congenital hypothyroidism in children
It is up to the government to vigorously promote iodized salt to eliminate endemic goiter, and local cretinism is also eliminated. Pregnant women can take potassium iodide (1 to 10 drops per day) in 3 to 4 months of pregnancy, or intramuscular injection. Iodine oil once 2ml, eat more iodine-containing foods, early diagnosis and treatment of endemic cretinism, those with low performance should start to supplement thyroid hormone within 3 months after self-generation, the principle is the same as sporadic cretinism, deaf Should be specially trained.
Complication
Congenital hypothyroidism complications in children Complications, pericardial effusion, pleural effusion
Frequent mental retardation, motor developmental disorders, short stature, enlarged heart, may be associated with pericardial effusion, pleural effusion, digestive tract dysfunction.
Symptom
Congenital hypothyroidism symptoms in children Common symptoms Newborn less neck short bone age delayed response slow sleepiness expression indifferent conduction block hair sparse pericardial effusion newborn crying
The main features are poor growth and development, low intelligence and reduced basal metabolic rate.
1. Newborns and infants: Most newborns have no symptoms and signs of hypothyroidism, but careful medical history and physical examination often reveal suspicious clues. For example, when the mother is pregnant, she often feels less fetal movement, has expired birth, has a swollen facial, and has rough skin and physiology. Sexual jaundice is delayed, drowsiness, less crying, low crying, poor appetite, poor suction, low body temperature, constipation, large anterior hernia, posterior fornix, abdominal distension, umbilical hernia, slow heart rate, low heart sound and so on.
2. Infants and childhood: Most congenital hypothyroidism often occurs after several months or 1 year of age due to developmental dysfunction. At this time, thyroxine deficiency is serious, symptoms are typical, thyroid hormone deficiency severity and duration and symptom severity closely related.
(1) Special face: large head, short neck, swollen face, edema of eyelids, wide eye distance, wide nose, wide tongue, large tongue, extended tongue, sparse hair, indifferent expression, slow response.
(2) nervous system dysfunction: low intelligence, memory, attention loss, motor development disorders, walking delay, often hearing loss, feeling slow, lethargy, severe mucinous edema, coma.
(3) Growth retardation: short stature, long body, short limbs, and poor bone age.
(4) low cardiovascular function: weak pulse, low heart sound, blunt heart, can be associated with pericardial effusion, pleural effusion, ECG low voltage, prolonged PR, conduction block and so on.
(5) Digestive tract dysfunction: poor appetite, bloating, constipation, dry stool, and reduced gastric acid.
Examine
Examination of congenital hypothyroidism in children
1. Thyroid function test: Plasma TSH and total T3, total T4 concentration is shown in Table 3 below, normal concentration of TBG is 160-750nmol/L, plasma T3, T4 is greatly affected by TBG, FT3 is measured, FT4 can better reflect thyroid function .
2. Thyroid-releasing hormone (TRH) stimulation test: For TSH with no increase in TSH, TRH stimulation test can be performed to understand the reserve function of pituitary. The patient is given intravenous injection of TRH 7g/kg, the maximum amount is not more than 200g, before and after injection. TSH content was determined by taking blood at 30 and 60 min respectively. TSH increased in a few minutes after normal injection of TRH, peaked at 20-30 min, returned to the baseline value at 90 min, and pituitary lesions should be considered when there is no reaction peak. TSH reaction peak is very high. Or prolonged duration, suggesting hypothalamic lesions.
3. Thyroid nuclides imaging (99mTc, 123I): can determine the location, size, development and iodine function of the thyroid, thyroid B ultrasound can also understand the location and size of the thyroid.
4. Determination of bone age: Bone age is a good indicator of maturity. It can be judged by X-ray film observation of the wrist, knee ossification center and osteophyte closure.
Diagnosis
Diagnosis and diagnosis of congenital hypothyroidism in children
diagnosis
Typical congenital hypothyroidism can be diagnosed according to clinical special performance, combined with X-ray examination and blood thyroid hormone determination.
At present, the screening of neonatal diseases that can be widely carried out can be diagnosed before congenital hypothyroidism, before the signs, but when the blood biochemistry has changed, an early diagnosis is made. The neonatal hypothyroidism is screened by dry blood filter paper. TSH was measured 3 days after birth to measure the heel capillary blood. It must be pointed out that TSH was used for neonatal disease screening, but hypothalamic-pituitary hypothyroidism could not be detected. In addition, no matter what screening method was used, due to experimental techniques Limitations, changes in physiological indicators and individual differences, a certain percentage of false negatives in neonatal disease screening, and negative cases in A low screening, such as clinical manifestations of hypothyroidism, should still be vigilant, for further details an examination.
Differential diagnosis
1.21 Trisomy Syndrome: Special face, hanging on the outer corner of the eye, suede in the eye, extension of the tip of the tongue, fine skin, soft hair, loose joints, distinct toe and Yu 4 toe, short middle section of the little finger, through the hand, Often associated with congenital heart disease, the chromosome is 21 triploid, and the thyroid function is normal.
2. Cartilage hypoplasia: one of the most common types of pygmy, due to cartilage ossification, mainly characterized by short limbs, especially the upper arm and thigh, the tip of the finger can not touch the femur big trochanter, the head is big, the big door Forehead protrusion, nose concave, often chicken breast and rib eversion, short separation, abdominal bulging, hip back, X-ray examination, all long bones become shorter, thicker, higher density, dry swell to both sides .
3. Hirschsprung's disease: clinical manifestations of intractable constipation, malnutrition, stunting, this disease is often misdiagnosed, congenital hypothyroidism as megacolon surgery, abdominal position flat film more low colonic obstruction, barium enema Typical sacral segments and dilated bowel segments were seen in the lateral radiographs, and blood T3, T4, and TSH were normal.
4. Mucopolysaccharidosis type I: This disease is a hereditary disease. The child is born with normal symptoms. The symptoms appear soon, the head is large, the bridge of the nose is flat, the tongue and lips are ugly, the cornea is cloudy, the hair is increased, and the liver and spleen are increased. Large, there are umbilical hernia, inguinal hernia, X-ray examination of the saddle becomes shallow, the anterior part of the vertebral body is wedge-shaped, the ribs are in the shape of a ribbon, the long bones are widened, the metacarpal bone, the phalanx is short, the mentality is backward, and the figure is short.
